A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses.

Humanized mice are limited in terms of modeling human immunity, particularly with regards to antibody responses. Here we constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated KitW-41J mutant immunodeficient pups with human cord blood CD34+ cells, followed by 17ß-estradiol conditioning to promote immune cell differentiation. THX mice reconstitute a human lymphoid and myeloid immune system, including marginal zone B cells, germinal center B cells, follicular helper T cells and neutrophils, and develop well-formed lymph nodes and intestinal lymphoid tissue, including Peyer's patches, and human thymic epithelial cells. These mice have diverse human B cell and T cell antigen receptor repertoires and can mount mature T cell-dependent and T cell-independent antibody responses, entailing somatic hypermutation, class-switch recombination, and plasma cell and memory B cell differentiation. Upon flagellin or a Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA vaccination, THX mice mount neutralizing antibody responses to Salmonella or severe acute respiratory syndrome coronavirus 2 Spike S1 receptor-binding domain, with blood incretion of human cytokines, including APRIL, BAFF, TGF-ß, IL-4 and IFN-γ, all at physiological levels. These mice can also develop lupus autoimmunity after pristane injection. By leveraging estrogen activity to support human immune cell differentiation and maturation of antibody responses, THX mice provide a platform to study the human immune system and to develop human vaccines and therapeutics.

Methods for the induction of labor: efficacy and safety.

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 µg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.

Predictive Value and Limitations of the Placenta Accreta Index: A Systematic Review.

Our systematic review highlights that multiparametric PAI score assessment is a consistent tool with high sensitivity and specificity for prenatal prediction for placenta accreta spectrum (PAS) in high-risk population with anterior placenta previa or low-lying placenta and prior cesarean deliveries. A systematic search was conducted on November 1, 2022, of MEDLINE via PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar to identify relevant studies (PROSPERO ID # CRD42022368211). A total of 11 articles met our inclusion criteria, representing the data of a total of 1,044 cases. Women with PAS had an increased mean PAI total score, compared to those without PAS. Limitations of the PAI are most studies were conducted in developing countries in high-risk population which limit the global generalizability of findings. Heterogeneity of reported data did not allow to perform meta-analysis.

Association between Antenatal Vaginal Bleeding and Adverse Perinatal Outcomes in Placenta Accreta Spectrum.

Background and Objectives: Placenta accreta spectrum (PAS) disorders are placental conditions associated with significant maternal morbidity and mortality. While antenatal vaginal bleeding in the setting of PAS is common, the implications of this on overall outcomes remain unknown. Our primary objective was to identify the implications of antenatal vaginal bleeding in the setting of suspected PAS on both maternal and fetal outcomes. Materials and Methods: We performed a case-control study of patients referred to our PAS center of excellence delivered by cesarean hysterectomy from 2012 to 2022. Subsequently, antenatal vaginal bleeding episodes were quantified, and components of maternal morbidity were assessed. A maternal composite of surgical morbidity was utilized, comprised of blood loss ≥ 2 L, transfusion ≥ 4 units of blood, intensive care unit (ICU) admission, and post-operative length of stay ≥ 4 days. Results: During the time period, 135 cases of confirmed PAS were managed by cesarean hysterectomy. A total of 61/135 (45.2%) had at least one episode of bleeding antenatally, and 36 (59%) of these had two or more bleeding episodes. Increasing episodes of antenatal vaginal bleeding were associated with emergent delivery (p < 0.01), delivery at an earlier gestational age (35 vs. 34 vs. 33 weeks, p < 0.01), and increased composite maternal morbidity (76, 84, and 94%, p = 0.03). Conclusions: Antenatal vaginal bleeding in the setting of PAS is associated with increased emergent deliveries, earlier gestational ages, and maternal composite morbidity. This important antenatal event may aid in not only counseling patients but also in the coordination of multidisciplinary teams caring for these complex patients.

Implementation and outcomes of a uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum.

BACKGROUND: Placenta accreta spectrum disorders are a continuum of placental pathologies with significant maternal morbidity and mortality. Morbidity is related to the overall degree of placental adherence, and thus patients with placenta increta or percreta represent a high-risk category of patients. Hemorrhage and transfusion of blood products represent 90% of placenta accreta spectrum morbidity. Both tranexamic acid and uterine artery embolization independently decrease obstetrical hemorrhage. OBJECTIVE: This study aimed to provide an evidence-based intraoperative protocol for placenta accreta spectrum management. STUDY DESIGN: This study was a pre- and postimplementation analysis of concomitant uterine artery embolization and tranexamic acid in cases of patients with antenatally suspected placenta increta and percreta over a 5-year period (2018-2022). For comparison, a 5-year (2013-2017) preimplementation group was used to assess the impact of the uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum. Patient demographics and clinically relevant outcomes were obtained from electronic medical records. RESULTS: A total of 126 cases were managed by the placenta accreta spectrum team, of which 66 had suspected placenta increta/percreta over the 10-year time period. Two patients were excluded from the postimplementation cohort because they did not undergo both interventions. Thus, 30 (30/64; 47%) were treated after implementation of the uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum, and 34 (34/64; 53%) preimplementation patients did not undergo uterine artery embolization or tranexamic acid infusion. With the uterine artery embolization and tranexamic acid protocol, operative times were longer (416 vs 187 minutes; P<.01), and patients were more likely to receive general anesthesia (80% vs 47%; P<.01). However, blood loss was reduced by 33% (2000 vs 3000 cc; P=.03), overall blood transfusion rates decreased by 51% (odds ratio, 0.05 [95% confidence interval, 0.001-0.20]; P<.01), and massive blood transfusion (>10 units transfused) was reduced 5-fold (odds ratio, 0.17 [95% confidence interval, 0.02-0.17]; P=.02). Postoperative complication rates remained unchanged (4 vs 10 events; P=.14). Neonatal outcomes were equivalent. CONCLUSION: The uterine artery embolization and tranexamic acid protocol for placenta accreta spectrum is an effective approach to the standardization of complex placenta accreta spectrum cases that results in optimal perioperative outcomes and reduced maternal morbidity.

Risk of Severe Maternal Morbidity in Patients with Placenta Accreta Spectrum Disorders Referred from Rural Communities to a Regional Placenta Accreta Spectrum Center.

OBJECTIVE: The primary objective of this study was to assess the risk of severe maternal morbidity (SMM) experienced by patients residing in rural communities when delivered by a multidisciplinary team within a single urban academic center for placenta accreta spectrum (PAS). Subsequently, we aimed to determine a distance-dependent relationship between PAS morbidity and distance travelled by patients in rural communities. STUDY DESIGN: This was a retrospective cohort study of patients who had PAS histopathological confirmation and delivery at our institution from 2005 to 2022. Our objective was to determine the relationship between patient locations (rural vs. urban) and maternal morbidity associated with PAS delivery. Sociogeographic determination of rurality was determined using the National Center for Health Statistics and most recent national census population data. Distance travelled was calculated by patient zip code to our PAS center using global positioning system data. RESULTS: During the study period, 139 patients were managed by cesarean hysterectomy with confirmed PAS histopathology. Of these, 94 (67.6%) were from our urban community and 45 (32.4%) were from surrounding rural communities. The overall SMM incidence was 85% including blood transfusion and 17% without blood transfusions. Patient from rural communities were more likely to experience SMM (28.9 vs. 12.8%, p = 0.03) and this was driven by acute renal failure (1.1 vs. 11.1%, p = 0.01) and disseminated intravascular coagulopathy (1.1 vs. 8.8%, p = 0.04). SMM did reveal a distance-dependent relationship with SMM rates of 13.2, 33.3, and 43.8% at 50, 100, and 150 miles, respectively (p = 0.005). CONCLUSION: Patients with PAS experience high rates of SMM. Geographic distance to a PAS center appears to significantly impact the overall morbidity a patient experiences. Further research is warranted to address this disparity and optimize patient outcomes for patients in rural communities KEY POINTS: · Patients from rural communities experience greater SMM in the setting of PAS.. · Intraoperative outcomes and interventions were similar, regardless of patient location.. · SMM may be related to the distance travelled by patients in rural communities..

Factors Limiting Magnetic Resonance Imaging Diagnosis of Placenta Accreta Spectrum.

OBJECTIVE: Placenta accreta spectrum (PAS) disorders are characterized by an abnormal adherence of the placenta to the uterine myometrium. Magnetic resonance imaging (MRI) is an important adjunct in antenatal diagnosis. We sought to determine if there are patient and MRI characteristics that limit the accuracy of PAS diagnosis and degree of invasion. STUDY DESIGN: We conducted a retrospective cohort analysis of patients who were evaluated for PAS by MRI from January 2007 to December 2020. Patient characteristics evaluated included number of prior cesarean deliveries, history of dilation and curettage (D&C) or dilation and evacuation (D&E), short interval pregnancy less than 18 months, and delivery body mass index (BMI). All patients were followed until delivery and MRI diagnosis was compared with final histopathology. RESULTS: Of the 353 patients with suspected PAS, 152 (43%) underwent MRI evaluation and were included in the final analysis. In patients who underwent MRI evaluation, 105 (69%) had confirmed PAS on pathology. Patient characteristics were similar between groups and not associated with accuracy of MRI diagnosis. MRI was accurate in diagnosing PAS and the associated degree of invasion in 83 (55%) patients. Accuracy was associated with lacunae (8 vs. 0%, p = 0.02), abnormal bladder interface (25 vs. 6%, p = 0.002), and T1 hyperintensity (13 vs. 1%, p = 0.002). Of the 69 (45%) patients in whom MRI was inaccurate, overdiagnosis was seen in 44 (64%) patients and underdiagnosis in 25 (36%) patients. Overdiagnosis was significantly associated with dark T2 bands (45 vs. 22%, p = 0.005). Underdiagnosis was associated with earlier gestational age at MRI (28 vs. 30 weeks, p = 0.049) and lateral placentation (16 vs. 2.4%, p = 0.025). CONCLUSION: Patient factors did not change MRI accuracy of PAS diagnosis. MRI is associated with a significant overdiagnosis of PAS when dark T2 bands are present, and underdiagnose PAS when performed earlier in gestation or when lateral placentation is present. KEY POINTS: · Patient factors are not associated with MRI accuracy of PAS diagnosis.. · MRI overdiagnoses PAS invasion when there are dark T2 bands.. · MRI underdiagnoses PAS invasion when performed earlier in gestation.. · Underdiagnosis of PAS is associated with lateral placentation..

Importance of the gynecologic oncologist in management of cesarean hysterectomy for Placenta Accreta Spectrum (PAS).

OBJECTIVE: Placenta Accreta Spectrum (PAS) is an invasive placental disorder characterized by significant maternal and fetal morbidity. Utilization of multidisciplinary teams has been shown to optimize patient outcomes. Our objective was to assess the impact of cesarean hysterectomy performed by gynecologic oncologists versus Ob/Gyn specialists in maternal morbidity. METHODS: A retrospective cohort study was performed of singleton, non-anomalous pregnancies complicated by PAS University of Texas Health San Antonio Placenta Accreta program from 2010 to 2021. Our primary outcome was a maternal morbidity composite of any of the following: estimated blood loss >2 L, ICU admission, intraoperative acidosis and post-operative length of stay >4 days. In addition, demographic and pregnancy data were obtained. Univariate and multivariate analyses were performed to identify the individual impact of variables such as general anesthesia, episodes of vaginal bleeding, uterine artery embolization, emergent delivery and placenta percreta pathology. RESULTS: 122 pregnancies complicated by PAS who underwent cesarean hysterectomy were identified from 2010 to 2021. Gynecologic oncologists were the primary surgeons for 62 (50.8%) of these cases. The involvement of gynecologic oncologists increased over the time period from 16% to 80%. Gynecologic oncologists were more like to be involved in cases with an antenatal diagnosis of placenta percreta (11.7 vs 37.1%, p = 0.001) and these cases were characterized by increased composite maternal morbidity (65 vs 83.9%, p = 0.02). These cases were also significantly longer (151 vs 271 min, p < 0.0001), involved greater usage of urinary stents (36.7 vs 66.1%, p = 0.002) and had longer post-operative lengths of stay (3 vs 4 days, p < 0.0001). PAS cesarean hysterectomies by gynecologic oncologists were less likely to be supracervical (25 vs 3.2%, p = 0.0005). Multivariate analysis controlling for placenta percreta, uterine artery embolization, vaginal bleeding and emergent delivery showed no difference in composite maternal morbidity (aOR = 0.95, 95%CI [0.35-2.52]) and lower rates of intraoperative acidosis (aOR = 0.36, 95%CI [0.14-0.93]) or post-operative length of stay >4 days (aOR = 0.37, 95%CI [0.15-0.91]). CONCLUSIONS: Gynecologic oncologists play a critical role in the surgical management of PAS cesarean hysterectomies. When compared to Ob/Gyn specialists, gynecologic oncologists are more likely to act as primary surgeons in complex cases similar morbidity and greater post-operative outcomes.

Health Burden and Service Utilization in Texas Medicaid Deliveries from the Prenatal Period to 1 Year Postpartum.

OBJECTIVE: To describe health burden and health service utilization from the prenatal period to 1 year postpartum among women with births covered by Texas Medicaid, focusing on the major contributors to maternal mortality after 60 days postpartum in Texas. METHODS: We analyzed diagnoses and health service utilization during the prenatal, early postpartum (5-60 days postpartum), and late postpartum (> 60 days to 1 year postpartum) periods, using administrative medical claims data for women ages 18-44 years with a Medicaid-paid delivery in 2017 residing in selected regions in Texas (n = 49,302). RESULTS: Overall, 12.6% and 17.5% of women had diagnoses of cardiovascular/coronary conditions and substance use disorder, respectively. Mental health conditions affected 30% of women, with anxiety (47.1%) and depression (34.3%) accounting for the greatest proportion of diagnosed mental health conditions. The prevalence of these conditions was higher during the late (19.4%) versus early (9.9%) postpartum period. About 47.8% of women had other chronic health conditions, including obesity, diabetes mellitus, and hypertension. Among women with the selected health conditions, utilization of any health services was higher during the prenatal period compared to early and late postpartum periods (e.g., any mental health service utilization: prenatal period (57.4%) versus early postpartum (26.9%) and late postpartum (25.5%) periods). However, among women with the selected health conditions, there was a high utilization of emergency room services during the late postpartum period [e.g., emergency room service utilization among those with mental health conditions: prenatal period (35.6%); postpartum period: early (5.5%) and late (30.1%)]. CONCLUSIONS FOR PRACTICE: Increasing access to the full range of recommended services during the prenatal period through 1 year postpartum has potential to help improve vulnerable women's birth outcomes.

Effect of anesthesia selection on neonatal outcomes in cesarean hysterectomies for placenta accreta spectrum (PAS).

OBJECTIVES: Optimal treatment for placenta accreta spectrum (PAS) is late-preterm cesarean hysterectomy to minimize maternal morbidity. This study aims to assess the impact of surgical planning during this gestational age on neonates as a key part of the pregnancy dyad. METHODS: A retrospective cohort analysis was performed of 115 singleton, non-anomalous pregnancies complicated by PAS at the University of Texas Health San Antonio Placenta Accreta program from 2005 to 2020. Univariate and multivariate analyses were performed to identify the individual impact of variables such as anesthesia selection, advancing gestational age and operative characteristics. RESULTS: With regards to neonatal intubation, on multivariate analysis, neuraxial anesthesia (OR=0.09, [95% CI 0.02, 0.37]) and advancing gestational age (OR=0.49 [95% CI 0.34, 0.71]) were independent protective factors. In addition, NICU length of stay was directly impacted by neuraxial anesthesia (IRR=0.73, [95% CI 0.55, 0.97]) and advancing gestational age (IRR=0.80 [95% CI 0.76, 0.84]), resulting in shorter NICU admissions. CONCLUSIONS: As gestational age at delivery may not be modifiable in cases of PAS, the utilization of neuraxial anesthesia (as oppose to general anesthesia) presents a modifiable intervention which may optimize neonatal outcomes from cesarean hysterectomy.

Elective Procedures in Obstetrics and Gynecology During the COVID-19 Pandemic.

The COVID-19 pandemic has stressed healthcare systems in the United States and globally. Limited hospital resources, increasing patient surge, and growing demands on healthcare providers have led to the United States Surgeon General and the Centers for Medicare & Medicaid Services calling for suspension of all nonessential adult elective surgery and medical procedures. As of March 27, 2020, 30 states had issued similar declarations related to elective procedures in the setting of the continuing COVID-19 pandemic. Two major questions have emerged as these events have unfolded: (1) What is the definition of an "elective" procedure? and (2) Are there specialty-specific considerations for obstetric and gynecologic procedures? This article provides insights into each of these questions and provides a working framework for obstetrician/gynecologists to advocate for their patients and coordinate with their hospital systems to develop "elective" procedure guidelines that incorporate considerations for women's and maternal health.

Maternal comorbidity index and severe maternal morbidity during delivery hospitalizations in Texas, 2011-2014.

BACKGROUND: Severe maternal morbidity (SMM) prevalence was 194.0 per 10 000 deliveries in Texas in 2015. Chronic, behavioral, and pregnancy-induced conditions, as captured by a maternal comorbidity index, increase the risk for delivery-related morbidity and mortality. The objective of the study was to examine the association between maternal comorbidity index and SMM among delivery hospitalizations in Texas. METHODS: Delivery-related hospitalizations among Texan women aged 15-49 years were identified using the 2011-2014 Texas all-payer inpatient hospitalization public use data files (n = 1 434 441). The primary outcome of interest was SMM, based on the Alliance for Innovation on Maternal Health's coding scheme. The exposure of interest was a maternal comorbidity index. Multivariable logistic regression model was used to examine the association between maternal comorbidity index and SMM. RESULTS: SMM prevalence remained consistent between 2011 and 2014 (196.0-197.0 per 10 000 deliveries, P > .05; n = 1 434 441). Nearly 40% of delivery-related hospitalizations had a maternal comorbidity index of at least 1, and the proportion of deliveries in the highest risk category of comorbidity index (≥5) increased by 12.0% from 2011 to 2014. SMM prevalence was highest among the youngest and oldest age groups. With each unit increase in maternal comorbidity index, the odds of SMM increase was 1.43 (95% CI 1.42-1.43). CONCLUSIONS: Maternal comorbidity index is associated with SMM; however, the low predictive power of the model suggests that other, unmeasured factors may influence SMM in Texas. These findings highlight a need to understand broader contextual factors (practitioner, facility, systems of care, and community) that may be associated with SMM to reduce maternal morbidity and mortality in Texas.

Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology.

BACKGROUND: Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, clinicians use progestogens (drugs that interact with the progesterone receptors), beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. This is an update of a review, last published in 2013. Since publication of the 2018 update of this review, we have been advised that the Ismail 2017 study is currently the subject of an investigation by the Journal of Maternal-Fetal & Neonatal Medicine. We have now moved this study from 'included studies' to 'Characteristics of studies awaiting classification' until the outcome of the investigation is known. OBJECTIVES: To assess the efficacy and safety of progestogens as a preventative therapy against recurrent miscarriage. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 July 2017) and reference lists from relevant articles, attempting to contact trial authors where necessary, and contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two reviewers assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Twelve trials (1,856 women) met the inclusion criteria. Eight of the included trials compared treatment with placebo and the remaining four trials compared progestogen administration with no treatment. The trials were a mix of multicenter and single-center trials, conducted in India, Jordan, UK and USA. In five trials women had had three or more consecutive miscarriages and in seven trials women had suffered two or more consecutive miscarriages. Routes, dosage and duration of progestogen treatment varied across the trials. The majority of trials were at low risk of bias for most domains. Ten trials (1684 women) contributed data to the analyses. The meta-analysis of all women, suggests that there may be a reduction in the number of miscarriages for women given progestogen supplementation compared to placebo/controls (average risk ratio (RR) 0.73, 95% confidence interval (CI) 0.54 to 1.00, 10 trials, 1684 women, moderate-quality evidence). A subgroup analysis comparing placebo-controlled versus non-placebo-controlled trials, trials of women with three or more prior miscarriages compared to women with two or more miscarriages and different routes of administration showed no clear differences between subgroups for miscarriage. None of the trials reported on any secondary maternal outcomes, including severity of morning sickness, thromboembolic events, depression, admission to a special care unit, or subsequent fertility. There was probably a slight benefit for women receiving progestogen seen in the outcome of live birth rate (RR 1.07, 95% CI 1.00 to 1.13, 6 trials, 1411 women, moderate-quality evidence). We are uncertain about the effect on the rate of preterm birth because the evidence is very low-quality (RR 1.13, 95% CI 0.53 to 2.41, 4 trials, 256 women, very low-quality evidence). No clear differences were seen for women receiving progestogen for the other secondary outcomes including neonatal death, fetal genital abnormalities or stillbirth. There may be little or no difference in the rate of low birthweight and trials did not report on the secondary child outcomes of teratogenic effects or admission to a special care unit. AUTHORS' CONCLUSIONS: For women with unexplained recurrent miscarriages, supplementation with progestogen therapy may reduce the rate of miscarriage in subsequent pregnancies.

Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology.

BACKGROUND: Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilized egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, clinicians use progestogens (drugs that interact with the progesterone receptors), beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage. This is an update of a review, last published in 2013. OBJECTIVES: To assess the efficacy and safety of progestogens as a preventative therapy against recurrent miscarriage. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (6 July 2017) and reference lists from relevant articles, attempting to contact trial authors where necessary, and contacted experts in the field for unpublished works. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two reviewers assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Thirteen trials (2556 women) met the inclusion criteria. Nine of the included trials compared treatment with placebo and the remaining four trials compared progestogen administration with no treatment. The trials were a mix of multicenter and single-center trials, conducted in Egypt, India, Jordan, UK and USA. In six trials women had had three or more consecutive miscarriages and in seven trials women had suffered two or more consecutive miscarriages. Routes, dosage and duration of progestogen treatment varied across the trials. The majority of trials were at low risk of bias for most domains. Eleven trials (2359 women) contributed data to the analyses.The meta-analysis of all women, suggests that there is probably a reduction in the number of miscarriages for women given progestogen supplementation compared to placebo/controls (average risk ratio (RR) 0.69, 95% confidence interval (CI) 0.51 to 0.92, 11 trials, 2359 women, moderate-quality evidence). A subgroup analysis comparing placebo-controlled versus non-placebo-controlled trials and different routes of administration showed no differences between subgroups for miscarriage. However, there appears to be a subgroup difference for miscarriage between women with three or more prior miscarriages compared to women with two or more miscarriages, with a more pronounced effect in women with three or more prior miscarriages. However, it should be noted that there was high heterogeneity in the subgroup of women with three or more prior miscarriages.None of the trials reported on any secondary maternal outcomes, including severity of morning sickness, thromboembolic events, depression, admission to a special care unit, or subsequent fertility.There was probably a slight benefit for women receiving progestogen seen in the outcome of live birth rate (RR 1.11, 95% CI 1.00 to 1.24, 7 trials, 2086 women, moderate-quality evidence). While the rate of preterm birth is probably reduced for women receiving progestogen, this outcome was mainly driven by one trial and thus should be interpreted with great caution (RR 0.59, 95% CI 0.39 to 0.89, 5 trials, 811 women, moderate-quality evidence). No clear differences were seen for women receiving progestogen for the other secondary outcomes of neonatal death or fetal genital abnormalities. A possible reduction in stillbirth was seen, but again this outcome was driven mainly by one trial and should be interpreted with caution (RR 0.38, 95% CI 0.24 to 0.58, 3 trials, 1199 women). There may be little or no difference in the rate of low birthweight and trials did not report on the secondary child outcomes of teratogenic effects or admission to a special care unit. AUTHORS' CONCLUSIONS: For women with unexplained recurrent miscarriages, supplementation with progestogen therapy probably reduces the rate of miscarriage in subsequent pregnancies.

Efficiency of Screening for the Recurrence of Antenatal Group B Streptococcus Colonization in a Subsequent Pregnancy: A Systematic Review and Meta-analysis with Independent Patient Data.

OBJECTIVE: The objective of this study was to evaluate the risk of recurrent group B streptococcus (GBS) colonization in a subsequent pregnancy and to assess clinical characteristics that influence this risk. STUDY DESIGN: A systematic review and meta-analysis was performed. Databases were searched from inception through June 2015 using PubMed, Embase, Scopus, Central, and ClinicalTrials.gov. Studies were eligible if they assessed antenatal GBS colonization in two successive pregnancies. The quality of included studies was evaluated. Independent patient data was requested from the authors of the included trials. Unadjusted odds ratios (OR) were pooled using the Mantel-Haenszel fixed effect model. RESULTS: In the five studies identified, two studies lacked a nonexposed cohort. GBS colonization in the index pregnancy was associated with a higher risk of recurrence of GBS colonization in a subsequent pregnancy (three studies: 50.2 compared with 14.1%; pooled fixed effects OR, 6.05; 95% confidence interval [CI], 4.84-7.55). When heavy colonization with GBS was compared with colonization by vaginal culture only, an increased risk of recurrence was shown (four studies: 52.0 compared with 45.1%, pooled fixed effects OR, 1.54; 95% CI, 1.02-2.31). CONCLUSION: Women colonized with GBS are at significantly higher odds for recurrent colonization in a subsequent pregnancy when compared with women who were not colonized in an index pregnancy. If the individual is considered heavily colonized with GBS, there appears to be an association with an increased risk compared with conventional culture. Subgroup analysis of the variables time interval ≤ 12 months between subsequent pregnancies, body mass index ≥ 30 kg/m(2), race, ethnicity, and primiparous in the subsequent pregnancy showed no effect.

Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy.

OBJECTIVE: We sought to determine predictors of adverse neonatal outcomes in women with intrahepatic cholestasis of pregnancy (ICP). STUDY DESIGN: This study was a multicenter retrospective cohort study of all women diagnosed with ICP across 5 hospital facilities from January 2009 through December 2014. Obstetric and neonatal complications were evaluated according to total bile acid (TBA) level. Multivariable logistic regression models were developed to evaluate predictors of composite neonatal outcome (neonatal intensive care unit admission, hypoglycemia, hyperbilirubinemia, respiratory distress syndrome, transient tachypnea of the newborn, mechanical ventilation use, oxygen by nasal cannula, pneumonia, and stillbirth). Predictors including TBA level, hepatic transaminase level, gestational age at diagnosis, underlying liver disease, and use of ursodeoxycholic acid were evaluated. RESULTS: Of 233 women with ICP, 152 women had TBA levels 10-39.9 µmol/L, 55 had TBA 40-99.9 µmol/L, and 26 had TBA ≥100 µmol/L. There was no difference in maternal age, ethnicity, or prepregnancy body mass index according to TBA level. Increasing TBA level was associated with higher hepatic transaminase and total bilirubin level (P < .05). TBA levels ≥100 µmol/L were associated with increased risk of stillbirth (P < .01). Increasing TBA level was also associated with earlier gestational age at diagnosis (P < .01) and ursodeoxycholic acid use (P = .02). After adjusting for confounders, no predictors were associated with composite neonatal morbidity. TBA 40-99.9 µmol/L and TBA ≥100 µmol/L were associated with increased risk of meconium-stained amniotic fluid (adjusted odds ratio, 3.55; 95% confidence interval, 1.45-8.68 and adjusted odds ratio, 4.55; 95% confidence interval, 1.47-14.08, respectively). CONCLUSION: In women with ICP, TBA level ≥100 µmol/L was associated with increased risk of stillbirth. TBA ≥40 µmol/L was associated with increased risk of meconium-stained amniotic fluid.

First trimester screening cannot predict adverse outcomes yet.

The use of first trimester screening to detect aneuploidy has become an integral part of prenatal care. The application of similar screening algorithms to identify women at the highest risk for other adverse pregnancy outcomes in the first trimester could potentially have a major clinical impact. There has been much investigation into the ability to identify patients early in pregnancy at high risk for adverse pregnancy outcomes who may benefit from further surveillance and/or intervention. For this to be the case, however, as is true of any useful screening test, effective interventions need to be available. Unfortunately, for fetal growth restriction and stillbirth, no such interventions exist short of delivery. For preeclampsia, low dose aspirin has been demonstrated to be of benefit in specific subgroups. For preterm birth, although there are efficacious treatments, first trimester serum markers or cervical length measurements do not add significantly beyond historical or demographic factors, in prediction of preterm birth. Given the current evidence, first trimester screening, via serum or ultrasound markers, does not have sufficiently high enough positive predictive values for the development of preeclampsia, fetal growth restriction, preterm birth or stillbirth. In order to develop effective screening algorithms for adverse pregnancy outcomes in the first trimester, understanding the heterogeneous phenotype of these complications and the underlying pathophysiology is needed.

An obstetric-specific surgical Apgar score predicts maternal morbidity from cesarean hysterectomy for placenta accreta spectrum.

OBJECTIVE: Placenta accreta spectrum (PAS) is a continuum of placental conditions characterized by significant maternal and neonatal morbidity. Tools to accurately predict postoperative morbidity have been lacking due to the hemodynamic changes of pregnancy. The surgical Apgar score (SAS) is a 10-point scale that assesses heart rate, mean arterial pressure, and estimated blood loss. The SAS has been validated to predict morbidity such as blood transfusion and reoperation. METHODS: We created an obstetric-specific SAS (ObSAS) scale for physiologic changes of pregnancy (two-fold increase in blood loss, 10% increased heart rate, and 5% decreased mean arterial pressure) and analyzed 110 cases of PAS who underwent cesarean hysterectomy. RESULTS: An ObSAS of 0-4 (poorest score) was significantly associated with increased risk of intensive care unit (ICU) admission (odds ratio [OR] 40.6, 95% confidence interval [CI] 7.9-742.9), transfusion >4 units (26/26 patients), and greater surgical morbidity (OR 22.7, 95% CI 4.4-415.0). ObSAS of 9-10 resulted in no ICU admissions (0/12), fewer blood transfusions (OR 0.1, 95% CI 0.1-0.4). and less surgical morbidity (OR 0.09, 95% CI 0.01-0.37). CONCLUSION: Given the overall surgical morbidity associated with PAS cesarean hysterectomy, the ObSAS score is a powerful tool with excellent predictive capabilities for ICU admission, blood transfusion, and surgical morbidity, allowing for resource allocation, prophylactic interventions, and optimal patient outcomes.

Extracorporeal Membrane Oxygenation in Pregnant and Postpartum Women With Critical Coronavirus Disease 2019 (COVID-19) Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the maternal survival and live-birth rates in pregnant women with acute respiratory distress syndrome (ARDS) secondary to critical coronavirus disease 2019 (COVID-19) who are treated with extracorporeal membrane oxygenation (ECMO) by performing a systematic review and meta-analysis. DATA SOURCES: From database inception through August 2023, we explored MEDLINE, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials. Studies reporting maternal survival and live-birth rates in pregnant women with critical COVID-19 undergoing ECMO were included. METHODS OF STUDY SELECTION: Two reviewers separately ascertained studies, obtained data, and evaluated study quality. Summary estimates of maternal survival and live-birth rates were measured, and 95% CIs were calculated. TABULATION, INTEGRATION, AND RESULTS: Nine retrospective case series and 12 retrospective cohort studies were identified with 386 pregnant women with critical COVID-19 who underwent ECMO. Studies evaluated women that were treated from January 2020 to October 2022. Four studies were from the United States; three were from Turkey; two were from France; two were from Israel; and one each was from Columbia, Germany, Italy, Kuwait, Poland, Republic of Srpska, the United Arab Emirates, the United Kingdom, a consortium from Belgium, France, Switzerland, and an international registry. The pooled estimate of the maternal survival rate among pregnant patients who were initiated on ECMO was 75.6% (95% CI, 66.0-84.1%, I2 =72%). The pooled estimate of the live-birth rate among pregnant patients who were initiated on ECMO was 83.7% (95% CI, 76.8-89.6%, 153 neonates, I2 =11%). When the case series and cohort studies were examined separately, the results were similar. CONCLUSION: Among pregnant women with acute respiratory distress syndrome attributable to critical COVID-19 who were managed with ECMO, maternal survival and live-birth rates were high. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023442800.

Hepatic infarction in pregnancy: a systematic review.

OBJECTIVE: Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this review is to identify risk factors, present signs and symptoms, identify methods of diagnosis, and identify best management practices on the basis of published case reviews. DATA SOURCES: PubMed and MEDLINE (Ovid) databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period from database inception until the study date of December 18, 2023. Key words included "liver infarction" or "hepatic infarction" and "pregnancy" or "obstetrics." STUDY ELIGIBILITY CRITERIA: Case reviews or case series published in the English language were included. Our study was registered with the Prospective Register of Systematic Reviews (registration number CRD42023488176) and was conducted in accordance with the published Prospective Register of Systematic Reviews and Meta-analyses Of Observational Studies in Epidemiology guidelines. METHODS: Included papers were evaluated for bias using a previously published tool. RESULTS: A total of 38 citations documenting 50 pregnancies published between 1979 and 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome, and 22% had a history of thrombus. Of those without a preexisting diagnosis of antiphospholipid syndrome, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%), and 32% and 16% had severe blood pressure or mild blood pressure, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm, and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. Computed tomography scans were used to confirm diagnosis of hepatic infarction in 58% of cases, magnetic resonance imaging in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases. CONCLUSION: Hepatic infarction should be considered in all cases of hemolysis, elevated liver enzymes, and low platelets syndrome, but specifically in patients with a history of antiphospholipid syndrome who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with a computed tomography scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.